3-38793966-G-A

Variant names:

• chr3-38793966-G-A
• rs34314583
• NM_006514.4:c.45C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_006514.4(SCN10A):​c.45C>T​(p.Arg15Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00836 in 1,613,980 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0065 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0086 (91 hom.)
• Consequence: SCN10A NM_006514.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.03
• Publications: 4 publications found

Genes affected

SCN10A (HGNC:10582): (sodium voltage-gated channel alpha subunit 10) The protein encoded by this gene is a tetrodotoxin-resistant voltage-gated sodium channel alpha subunit. The properties of the channel formed by the encoded transmembrane protein can be altered by interaction with different beta subunits. This protein may be involved in the onset of pain associated with peripheral neuropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

SCN10A Gene-Disease associations (from GenCC):

• sodium channelopathy-related small fiber neuropathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• episodic pain syndrome, familial, 2

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
• Brugada syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Genomics England PanelApp
• Brugada syndrome 1

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 3-38793966-G-A is Benign according to our data. Variant chr3-38793966-G-A is described in ClinVar as Benign. ClinVar VariationId is 240676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.03 with no splicing effect.
• BS2: High AC in GnomAd4 at 984 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006514.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN10A	NM_006514.4	MANE Select	c.45C>T	p.Arg15Arg	synonymous	Exon 2 of 28	NP_006505.4
	SCN10A	NM_001293306.2		c.45C>T	p.Arg15Arg	synonymous	Exon 1 of 27	NP_001280235.2
	SCN10A	NM_001293307.2		c.45C>T	p.Arg15Arg	synonymous	Exon 1 of 26	NP_001280236.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN10A	ENST00000449082.3	TSL:1 MANE Select	c.45C>T	p.Arg15Arg	synonymous	Exon 2 of 28	ENSP00000390600.2
	SCN10A	ENST00000643924.1		c.45C>T	p.Arg15Arg	synonymous	Exon 1 of 27	ENSP00000495595.1
	SCN10A	ENST00000655275.1		c.45C>T	p.Arg15Arg	synonymous	Exon 2 of 28	ENSP00000499510.1

Frequencies

GnomAD3 genomes AF: 0.00647 AC: 985 AN: 152192 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0142

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00587 AC: 1473 AN: 250830 AF XY: 0.00558

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00402

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0124

Gnomad NFE exome AF: 0.00885

Gnomad OTH exome AF: 0.00441

GnomAD4 exome AF: 0.00856 AC: 12508 AN: 1461670 Hom.: 91 Cov.: 31 AF XY: 0.00839 AC XY: 6100 AN XY: 727144

African (AFR) AF: 0.00143 AC: 48 AN: 33468

American (AMR) AF: 0.00407 AC: 182 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26126

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.000243 AC: 21 AN: 86258

European-Finnish (FIN) AF: 0.0118 AC: 629 AN: 53416

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.0102 AC: 11302 AN: 1111840

Other (OTH) AF: 0.00523 AC: 316 AN: 60384

GnomAD4 genome AF: 0.00646 AC: 984 AN: 152310 Hom.: 4 Cov.: 32 AF XY: 0.00635 AC XY: 473 AN XY: 74484

African (AFR) AF: 0.00152 AC: 63 AN: 41572

American (AMR) AF: 0.00366 AC: 56 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.0142 AC: 151 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0103 AC: 703 AN: 68014

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00831 Hom.: 1

Bravo AF: 0.00539

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00676

EpiControl AF: 0.00842

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	1	Brugada syndrome (1)
-	-	1	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.5
DANN	Benign	0.54
PhyloP100		-1.0
PromoterAI		0.026	Neutral
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34314583; hg19: chr3-38835457;